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Michael Jiang,1 Varun Peri,1 Bobby Ou Yang,1 Jaewon Chang,2 Douglas Hacking1 1Department of Anaesthesia, Austin Health, Melbourne, Victoria, Australia; 2Department of Surgery, St George Hospital, Sydney, New South Wales, AustraliaCorrespondence: Michael Jiang, Department of Anaesthesia, Austin Health, 145 Studley Road, Heidelberg, 3084, Victoria, Australia, Email Michael.jiang49@gmail.comIntroduction: Rib fractures are a common sequelae of chest trauma and are associated with significant morbidity. The erector spinae nerve block (ESB) has been proposed as an alternative first-line regional technique for rib fractures due to ease of administration and minimal complication profile. We aimed to investigate the current literature surrounding this topic with a focus on pain and respiratory outcomes.Methods: A comprehensive literature search was performed on the Medline, Embase, Web of Science, Scopus, and Cochrane databases. Keywords of “erector spinae block” and “rib fractures” were used to form the search strategy. Papers published in English investigating ESB as an analgesic intervention for acute rib fracture were included. Exclusion criteria were operative rib fixation, or where the indication for ESB was not rib fracture.Results: There were 37 studies which met the inclusion criteria for this scoping review. Of these, 31 studies reported on pain outcomes and demonstrated a 40% decrease in pain scores post administration within the first 24 hours. Respiratory parameters were reported in 8 studies where an increase in incentive spirometry was demonstrated. Respiratory complication was not consistently reported. ESB was associated with minimal complications; only 5 cases of haematoma and infection were (incidence 0.6%) reported, none of which required further intervention.Discussion: Current literature surrounding ESB in rib fracture management provides a positive qualitative evaluation of efficacy and safety. Improvements in pain and respiratory parameters were almost universal. The notable outcome from this review was the improved safety profile of ESB. The ESB was not associated with complications requiring intervention even in the setting of anticoagulation and coagulopathy. There still remains a paucity of large cohort, prospective data. Moreover, no current studies reflect an improvement in respiratory complication rates compared to current techniques. Taken together, these areas should be the focus of any future research.Keywords: chest trauma, thoracic injury, regional anaesthesia, nerve block

We present the first results from a reverberation-mapping campaign undertaken during the first half of 2012, with additional data on one active galactic nucleus (AGN) (NGC 3227) from a 2014 campaign. Our main goals are (1) to determine the black hole masses from continuum-Hβ reverberation signatures, and (2) to look for velocity-dependent time delays that might be indicators of the gross kinematics of the broad-line region. We successfully measure Hβ time delays and black hole masses for five AGNs, four of which have previous reverberation mass measurements. The values measured here are in agreement with earlier estimates, though there is some intrinsic scatter beyond the formal measurement errors. We observe velocity-dependent Hβ lags in each case, and find that the patterns have changed in the intervening five years for three AGNs that were also observed in 2007.

We present optical continuum lags for two Seyfert 1 galaxies, MCG+08-11-011 and NGC 2617, using monitoring data from a reverberation mapping campaign carried out in 2014. Our light curves span the ugriz filters over four months, with median cadences of 1.0 and 0.6 days for MCG+08-11-011 and NGC 2617, respectively, combined with roughly daily X-ray and near-UV data from Swift for NGC 2617. We find lags consistent with geometrically thin accretion-disk models that predict a lag-wavelength relation of τ ∝ λ 4/3. However, the observed lags are larger than predictions based on standard thin-disk theory by factors of 3.3 for MCG+08-11-011 and 2.3 for NGC 2617. These differences can be explained if the mass accretion rates are larger than inferred from the optical luminosity by a factor of 4.3 in MCG+08-11-011 and a factor of 1.3 in NGC 2617, although uncertainty in the SMBH masses determines the significance of this result. While the X-ray variability in NGC 2617 precedes the UV/optical variability, the long (2.6 day) lag is problematic for coronal reprocessing models.

We present the first results from an optical reverberation mapping campaign executed in 2014 targeting the active galactic nuclei (AGNs) MCG+08-11-011, NGC 2617, NGC 4051, 3C 382, and Mrk 374. Our targets have diverse and interesting observational properties, including a "changing look" AGN and a broad-line radio galaxy. Based on continuum-Hβ lags, we measure black hole masses for all five targets. We also obtain Hγ and He ii λ4686 lags for all objects except 3C 382. The He ii λ4686 lags indicate radial stratification of the BLR, and the masses derived from different emission lines are in general agreement. The relative responsivities of these lines are also in qualitative agreement with photoionization models. These spectra have extremely high signal-to-noise ratios (100-300 per pixel) and there are excellent prospects for obtaining velocity-resolved reverberation signatures.

We present the results of an optical spectroscopic monitoring program targeting NGC 5548 as part of a larger multiwavelength reverberation mapping campaign. The campaign spanned 6 months and achieved an almost daily cadence with observations from five ground-based telescopes. The Hβ and He ii λ4686 broad emission-line light curves lag that of the 5100 +-optical continuum by 4.17+0.36-0.36 and 0.79+0.35-0.34 days, respectively. The Hβ lag relative to the 1158 ultraviolet continuum light curve measured by the Hubble Space Telescope is ∼50% longer than that measured against the optical continuum, and the lag difference is consistent with the observed lag between the optical and ultraviolet continua. This suggests that the characteristic radius of the broad-line region is ∼50% larger than the value inferred from optical data alone. We also measured velocity-resolved emission-line lags for Hβ and found a complex velocity-lag structure with shorter lags in the line wings, indicative of a broad-line region dominated by Keplerian motion. The responses of both the Hβ and He ii emission lines to the driving continuum changed significantly halfway through the campaign, a phenomenon also observed for C iv, Lyα, He ii(+O iii]), and Si iv(+O iv]) during the same monitoring period. Finally, given the optical luminosity of NGC 5548 during our campaign, the measured Hβ lag is a factor of five shorter than the expected value implied by the R BLR-L AGN relation based on the past behavior of NGC 5548.

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Introduction: Many studies have shown that monocyte human leukocyte antigen-DR (mHLA-DR) expression may be a good predictor for mortality in severe septic patients. On the contrary, other studies found mHLA-DR was not a useful prognostic marker in severe sepsis. Few studies have taken changes of mHLA-DR during treatment into consideration. The objective of this study was to estimate the prognostic value of changes of mHLA-DR to predict mortality in severe sepsis.Methods: In this prospective observational study, mHLA-DR was measured by flow cytometry in peripheral blood from 79 adult patients with severe sepsis. mHLA-DR levels were determined on day 0, 3, 7 after admission to the surgical intensive care unit (SICU) with a diagnosis of severe sepsis. ΔmHLA-DR₃ and ΔmHLA-DR₇ were defined as the changes in mHLA-DR value on day 3 and day 7 compared to that on day 0. Data were compared between 28-day survivors and non-survivors. Receiver operating characteristic (ROC) curves were plotted to measure the performance and discriminating threshold of ΔmHLA-DR₃, ΔmHLA-DR₇, ΔmHLA-DR₇-₃, mHLA-DR₀, mHLA-DR₃ and mHLA-DR₇ in predicting mortality of severe sepsis.Results: ROC curve analysis showed that ΔmHLA-DR₃ and ΔmHLA-DR7 were reliable indicators of mortality in severe sepsis. A ΔmHLA-DR₃ value of 4.8% allowed discrimination between survivors and non-survivors with a sensitivity of 89.0% and a specificity of 93.7%; similarly, ΔmHLA-DR₇ value of 9% allowed discrimination between survivors and non-survivors with a sensitivity of 85.7% and a specificity of 90.0%. Patients with ΔmHLA-DR₃ ≤ 4.8% had higher mortality than those with ΔmHLA-DR₃ > 4.8% (71.4% vs. 2.0%, OR 125.00, 95% CI 13.93 to 1121.67); patients with ΔmHLA-DR7 ≤ 9% had higher mortality than those with ΔmHLA-DR₇ > 9% (52.9% vs. 2.0%, OR 54.00, 95% CI 5.99 to 486.08). The mean change of mHLA-DR significantly increased in the survivor group with the passage of time; from day 0 to day 3 and day 7, changes were 6.45 and 16.90 (P < 0.05), respectively.Conclusions: The change of mHLA-DR over time may be a reliable predictor for mortality in patients with severe sepsis. [ABSTRACT FROM AUTHOR]

Objective: To develop age-appropriate nonaGEnaRIan And cenTenarian suRgICal (GERIATRIC) risk tool for classifying patients who may or may not develop postoperative complications or die within their index hospital admission., Background: There are no validated perioperative risk stratification tools for use in nonagenarian and centenarian patients-people aged 90 to 99 years and >100 years., Methods: In this retrospective observational study, nonagenarians and centenarians undergoing any surgical procedure were profiled. Surgery severity was stratified, and the incidence and grade of postoperative complications were recorded. Multivariable logistic regression analysis was performed on a training cohort, followed by calibration on a validation cohort, followed by performance evaluation on a testing cohort. The discriminative accuracy was compared to that of the age-adjusted Charlson Comorbidity Index for each outcome. The primary outcome was the ability of the risk stratification tool to effectively classify patients into those who may or may not experience a postoperative complications or mortality within their index hospital stay., Results: A total of 3085 patients were enrolled. The GERIATRIC risk tool had good discriminative accuracy for any postoperative complication [area under the receiver operating characteristic curves (AUROC), 0.857; 95% CI = 0.824-0.890] and any severe postoperative complication (AUROC, 0.833; 95% CI = 0.793-0.874), and fair discriminative accuracy for in-hospital mortality (AUROC, 0.780; 95% CI = 0.668-0.893)., Conclusions: Compared to the age-adjusted Charlson Comorbidity Index, The GERIATRIC risk tool was accurate in classifying patients into those who may or may not experience severe complications or die during their index admission. The tool can be used to assist perioperative clinicians with shared decision-making and short-term prognostication., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Anaemia following major surgery may be associated with unplanned readmission to hospital. However, the severity-response relationship between the degree of anaemia at discharge and the risk of unplanned readmission is poorly defined. We aimed to describe the severity-response relationship between haemoglobin concentration at the time of discharge and the risk of unplanned readmission in a cohort of patients undergoing different types of major surgery., Methods: We performed a retrospective cohort study in a single tertiary health service, including all patients who underwent major surgery (orthopaedic, abdominal, cardiac or thoracic) between 1 May 2011 and 1 February 2022. The primary outcome was unplanned readmission to hospital in the 90 days following discharge after the index surgical procedure. These complex, non-linear relationships were modelled with restricted cubic splines., Results: We identified 22,134 patients and included 14,635 in the primary analysis, of whom 1804 (12%) experienced at least one unplanned readmission. The odds of unplanned readmission rose when the discharge haemoglobin concentration was < 100 g.l -1 (p < 0.001). On subgroup analysis, the haemoglobin threshold below which odds of readmission began to increase appeared to be higher in patients undergoing emergency surgery (110 g.l -1 ; p < 0.001) compared with elective surgery. Declining discharge haemoglobin concentration was associated with increased odds ratios (95%CI) of unplanned readmission in patients undergoing orthopaedic (1.08 (1.01-1.15), p = 0.03), abdominal (1.13 (1.07-1.19), p < 0.001) and thoracic (1.12 (1.01-1.24), p = 0.03) procedures, but not cardiac surgery (1.09 (0.99-1.19), p = 0.07)., Conclusions: Our findings suggest that a haemoglobin concentration < 100 g.l -1 following elective procedures and < 110 g.l -1 following emergency procedures, at the time of hospital discharge after major surgery, was associated with unplanned readmission. Future interventional trials that aim to treat postoperative anaemia and reduce unplanned readmission should include patients with discharge haemoglobin below these thresholds., (© 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Adverse early life experiences, such as maternal separation, are associated with an increased risk for several mental health problems. Symptoms induced by maternal separation that mirror clinically relevant aspects of mental problems, such as cognitive inflexibility, open the possibility of testing putative therapeutics prior to clinical development. Although several animal (e.g., rodent) studies have evaluated the effects of early maternal separation on cognitive flexibility, no consistent conclusions have been drawn. To clarify this issue, in this study, a meta-analysis method was used to systematically explore the relationship between early maternal separation and cognitive flexibility in rodent offspring. Results indicate that early maternal separation could significantly impair cognitive flexibility in rodent offspring. Moderator analyses further showed that the relationship between early maternal separation and cognitive flexibility was not consistent in any case, but was moderated by variations in the experimental procedures, such as the deprivation levels, task characteristics, and rodent strains. These clarify the inconsistent effects of maternal separation on cognitive flexibility in rodents and help us better understand the association between early life adversity and cognitive development., (Copyright © 2022. Published by Elsevier Ltd.)

Numerous studies have revealed that an enriched environment can enhance the survival-related behaviors and brain functions of animals. However, the effects and specific roles of the enrichment characteristics on animals' innovative capability, a cognitive ability crucial for survival in nature, are still not well known. In this study, we assigned mice to environment-manipulation groups ( n = 15 each) to investigate the specific effects of environmental novelty (novel vs. familiar) and environmental complexity (complex vs. normal) on innovative problem solving and its possible neural mechanisms. Results showed that mice in only the novel-environment group performed better at innovative-problem-solving tasks and showed greater numbers of novel explorations and dopaminergic projections from the ventral tegmental area to the nucleus accumbens in the brain. These findings indicate that an enriched environment has the potential to promote the innovative capability of mice by enhancing their novel exploratory motivation, which depends on the novelty of the environment but not its complexity.

Background: The outcomes of nonagenarian patients undergoing orthopaedic surgery are not well understood. We investigated the 30-day mortality after surgical treatment of unilateral hip fracture. The relationship between postoperative complications and mortality was evaluated., Methods: We performed a single-centre retrospective cohort study of nonagenarian patients undergoing hip fracture surgery over a 6-year period. Postoperative complications were graded according to the Clavien-Dindo classification. Correlation analyses were performed to evaluate the relationship between mortality and pre-specified mortality risk predictors. Survival analyses were assessed using Cox proportional hazards regression modelling., Results: The study included 537 patients. The 30-day mortality rate was 7.4%. The mortality rate over a median follow-up period of 30 months was 18.2%. Postoperative complications were observed in 459 (85.5%) patients. Both the number and severity of complications were related to mortality (p < 0.001). Compared to patients who survived, deceased patients were more frail (p = 0.034), were at higher ASA risk (p = 0.010) and were more likely to have preoperative congestive heart failure (p < 0.001). The adjusted hazard ratio for mortality according to the number of complications was 1.3 (95% CI 1.1, 1.5; p = 0.003). Up to 21 days from admission, any increase in complication severity was associated significantly greater mortality [adjusted hazard ratio: 3.0 (95% CI 2.4, 3.6; p < 0.001)]., Conclusion: In a nonagenarian cohort of patients undergoing hip fracture surgery, 30-day mortality was 7.4%, but 30-month mortality rates approached one in five patients. Postoperative complications were independently associated with a higher mortality, particularly when occurring early., (© 2021. The Author(s).)

Objective This study analysed screening for COVID-19 before surgery and outcomes of any perioperative testing for SARS-CoV-2 infection during pandemic-restricted surgery. Methods An audit was conducted with routinely collected health data before both elective and non-elective surgery at two large Melbourne hospitals during April and early May 2020. We looked for documented systematic screening for COVID-19 disease and fever (>38°C) and results of SARS-COV-2 testing, and proposed a minimum acceptable documenting rate of 85%. Results The study included 2197 consecutive patients (1279 (58%) undergoing elective surgery, 917 (42%) undergoing non-elective surgery) across most specialities. Although 926 (72%) patients undergoing elective surgery had both systematic screening and temperature documented, approximately half that percentage undergoing non-elective surgery (n=347; 38%) had both documented. However, 871 (95%) of non-elective surgery patients had temperature documented. Acknowledging limited screening, 85 (9.3%) non-elective surgery patients had positive screening, compared with 39 (3.0%) elective surgery patients. All 152 (7%) patients who were tested for SARS-CoV-2 were negative, and no cases were reported from external contact tracing. Conclusions Although 'not documented' does not necessarily equal 'not done', we found that documenting of COVID-19 screening could be improved. Better understanding of implementing screening practices in pandemics and other crises, particularly for non-elective surgery patients, is warranted. What is known about the topic? Little is known about routine screening for SARS-CoV-2 infection among surgical patients. However, it is well established that implementing effective uptake of safety and quality initiatives can be difficult. What does this paper add? We found that although most patients had documented temperature, fewer than 75% had a documented systematic questionnaire screen for COVID, particularly patients undergoing non-elective surgery. What are the implications for practitioners? Clear documenting is important in managing patients. Pandemics and other crises can require rapid changes in practice. Implementing such measures may be less complete than anticipated and may require greater use of evidence-based implementation strategies, particularly in the less predictable care of non-elective surgery patients.

Objective: To explore the feasibility and effectiveness of gastric antrum cross-sectional area (CSA) mearsured by bedside ultrasound for predicting early feeding intolerance (FI) in critically ill patients., Methods: The data were extracted from a multicenter prospective observation study between February 2018 to December 2018. A bivariate logistic regression model was established to identify the correlation between the gastric antrum cross-sectional area (CSA) and the feeding intolerance (FI). Draw the ROC curve to get the best cut-off value., Results: This study comprises 150 patients. The mean age was (58.63±16.45) yr., the average APACHE Ⅱ score was 17.43±6.99. The incidence of FI for three days (72 h-FI%) was 28.0%. The multivariate analysis demonstrated that the Day 2 CSA-right lateral decubitus (RLD) was an independent risk factor for FI-day 2 ( P =0.033), Day 3 CSA -RLD was an independent risk factor for FI-day 3 ( P =0.016). Patients with day 3 CSA-RLD ≥7.092 cm 2 had significantly higher rates of FI ( P =0.001)., Conclusion: Gastric antrum cross-sectional area measured by ultrasound can predict feeding intolerance during early enteral nutrition. When the Day 3 CSA-RLD is greater than 7.092 cm 2 , the incidence of feeding intolerance is significantly increased., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Objective: To study the clinical application value of the penile erectile strength measurement (PESM) band in the differentiation of psychogenic from organic erectile dysfunction (ED)., Methods: Eighty ED patients unable to achieve or maintain adequate penile erection to complete sexual intercourse were included in the experimental group and another 40 healthy subjects with normal erectile function enrolled as controls. The ED cases were classified into mild, moderate and severe ED according to the IIEF-5 scores and divided into psychogenic and organic ED based on the results of the nocturnal penile tumescence (NPT) test. Then all the subjects underwent a three-night continuous monitoring with the PESM band and, according to the band fracture rate, the ED cases were also classified into psychogenic and organic ED. The rates of missed diagnosis, misdiagnosis and diagnostic coincidence of PESM were calculated with the results of NPT as the standard for differentiating psychogenic from organic ED., Results: The results of NPT tests revealed 51 cases of psychogenic and 29 cases of organic ED in the experimental group. The band fracture rate in PESM was 95.0% in the mild, 80.9% in the moderate and 52.8% in the severe ED patients. Of the 51 cases of psychogenic ED detected by NPT test, 43 were diagnosed as psychogenic and the other 8 as organic ED with the PESM band, with a coincidence rate of 84.3%. Of the 29 cases of organic ED revealed by NPT test, 5 were diagnosed as psychogenic and the other 24 as organic ED by PESM, with a coincidence rate of 82.8%. Normal erectile function with three-level fracture of the band was observed in the PESM of the normal controls, which showed a coincidence rate of 100% with the results of NPT tests. Based on the standard of the NPT test, the rates of missed diagnosis, misdiagnosis and diagnostic coincidence of the PESM band in differentiating psychogenic from organic ED were 15.7%, 17.2%, and 83.8%, respectively, with a Kappa value of 0.656 (P <0.05)., Conclusions: The penile erectile strength measurement band can be used as a screening tool for initial differentiation of psychogenic from organic ED.

Objective: To investigate the association of circumcision with the incidence of human papillomavirus (HPV) infection in men., Methods: We collected the samples from the surface of the coronal sulcus, glans penis, penile shaft and scrotum of 351 males examined for HPV infection in our hospital from January 2016 to August 2017, of whom 118 had received circumcision while the other 233 had not. We compared the incidence rate of HPV infection between the circumcision and non-circumcision groups and analyzed the association of the age of circumcision with the incidence of HPV infection., Results: HPV infection was found in 135 (38.46%) of the males, 29 (24.58%) in the circumcision group and 106 (45.49%) in the non-circumcision group, significantly lower in the former than in the latter (χ² = 14.48, P < 0.01). The incidence rate of HPV infection was also remarkably lower in the males circumcised at ≤17 years (13.16% ［5/38］) than in those circumcised at >17 years of age (30.0% ［24/80］) (χ² = 3.942, P = 0.047)., Conclusions: Male circumcision helps reduce the incidence rate of HPV infection in men and earlier surgery may achieve even better effect.

Objective: To make a real-world study on the efficacy and safety of traditional Chinese medicine (TCM) combined with sildenafil in the treatment of erectile dysfunction (ED) that failed to respond to TCM medication., Methods: This study included 1 038 ED patients with the International Index of Erectile Function-5 (IIEF-5) scores ≤21 and improvement <30% after 4 weeks of TCM medication, differentially diagnosed with kidney-yang or kidney-yin deficiency syndrome. We administered TCM combined with sildenafil (Viagra, Pfizer Pharmaceutical Co., Ltd) at 100 mg 1 hour before sexual intercourse. After 2 and 4 weeks of medication, we recorded the scores in IIEF-5, erection hardness, Sexual Encounter Profile question 2 (SEP-2: whether vaginal penetration is successful), SEP-3 (whether sexual intercourse is successful), and TCM Syndromes Scale as well as the indexes of routine blood, urine, liver function, and renal function of the patients, and compared them with those obtained before treatment., Results: No serious adverse reactions were observed in any of the patients. Compared with the baseline, the patients achieved significantly increased IIEF-5 scores after 2 and 4 weeks of medication (15.01 ± 2.25 vs 16.96 ± 2.55 and 19.41 ± 2.82, P <0.05), penileelectionhardness remarkably improved at 4 weeks (3.36% vs 44.58%, P<0.05), and the positive answers to SEP-2 and SEP-3 both markedly increased at 2 (38.11% vs 90.49%, P<0.05; 22.01% vs 63.77% , P<0.05) and 4 weeks (38.11% vs 96.95% , P<0.05; 22.01% vs 89.73%, P<0.05)., Conclusions: TCM combined with sildenafil is safe and effective in the treatment of ED in Chinese men, which can significantly improve the IIEF-5 score and erection hardness of the patients.

Objective: To investigate the values of serum calculated free testosterone (cFT), testosterone secretion index (TSI), and free testosterone index (FTI) in the diagnosis of ED with androgen deficiency by observing their changes in the patient., Methods: We conducted this study among 185 men complaining of ED and 35 20－40 years old healthy males presenting at the clinic for premarital medical checkup. We asked them about their medical history, to fill in the International Index of Erectile Function (IIEF-5) Questionnaire, and to complete the nocturnal penile tumescence (NPT) test. According to the data obtained, 150 of the complainants were diagnosed as ED patients and 25 of the healthy examinees were included in the control group. We determined the levels of total serum testosterone (TT), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), serum albumin (ALB), cFT, bio-available testosterone (bio-T), TSI, and FTI in the two groups of subjects. Using cFT ≤0.3 nmol/L, TSI ≤2.8, and FTI ≤0.4 as the critical values and TT ≤11.5 nmol/L as the gold standard for androgen deficiency, we calculated cFT-, TSI-, and FTI-related rates of missed diagnosis, misdiagnosis, and diagnostic coincidence., Results: With TT ≤11.5 nmol/L as the criterion, the cFT-, TSI-, and FTI-related rates of coincidence in the diagnosis of androgen deficiency in the ED patients were 90.8%, 85.8%, and 80.8%, those of missed diagnosis were 4.0%, 33.3%, and 44.0%, and those of misdiagnosis were 10.5%, 19.4%, and 12.6%, with the Kappa of values 0.755, 0.564, and 0.427, respectively (P <0.05). The levels of serum TT, cFT, Bio-T, TSI, and FTI were decreased with increased age of the 20－40 years old ED patients, with statistically significant differences among different age groups except the serum TT level. However, no statistically significant differences were found in the levels of TT, cFT, Bio-T, TSI, and FTI among the patients with different IIEF-5 scores., Conclusions: The level of cFT has a higher value than those of TT, TSI, and TSI in the diagnosis of ED with androgen deficiency in 20－40 years old men.

Background: Microbial lipid is a potential raw material for large-scale biodiesel production and lignocellulosic hydrolysate has been considered as promising low-cost substrate for lipid fermentation. Lignocellulosic biomass needs to be pretreated before enzymatic hydrolysis, and biocompatible cholinium ionic liquids (ILs) have been demonstrated to be highly efficient for pretreatment. However, the impact of these ILs residues in hydrolysates on downstream biotransformation remains unknown. Therefore, the influence of three typical cholinium ILs on the lipid production by Trichosporon fermentans was first investigated., Results: The cell growth of T. fermentans was stimulated in the presence of cholinium lysine ([Ch][Lys]) and cholinium serine ([Ch][Ser]), while the lipid accumulation was inhibited by [Ch][Lys]) and [Ch][Ser]. Both cell growth and lipid accumulation of T. fermentans were inhibited in the presence of cholinium acetate ([Ch][OAc]). Despite the reduction in lipid content, the lipid production by T. fermentans was improved in the presence of low concentrations of [Ch][Lys] (≤30 mM) and [Ch][Ser] (≤20 mM) due to the remarkable increase of biomass. It was found that cholinium cation had minor influence on lipid production. However, the anions of [Ch][Lys] and [Ch][Ser] could be assimilated as nitrogen source by T. fermentans and the reduced C/N ratio accounts for the inhibition of lipid accumulation, which could be alleviated by improving C/N ratio of medium. In addition, the anion of [Ch][OAc] could be metabolized by T. fermentans, leading to a rapid alkaline-pH shift and strong inhibition of lipid production. And this inhibitory effect on lipid production could be significantly reduced by controlling culture pH., Conclusions: The anions of [Ch][Lys], [Ch][Ser] and [Ch][OAc] play an important role in affecting the cell growth and lipid accumulation of T. fermentans, and the inhibition of these three ILs on lipid production can be alleviated by careful fermentation condition control. Hence, T. fermentans is a promising strain for microbial lipid production from cholinium ILs-pretreated lignocellulosic hydrolysates.

Introduction: Severe sepsis is associated with a high mortality rate despite implementation of guideline recommendations. Adjunctive treatment may be efficient and require further investigation. In light of the crucial role of immunologic derangement in severe sepsis, thymosin alpha 1 (Tα1) is considered as a promising beneficial immunomodulatory drug. The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis., Methods: We performed a multicenter randomized controlled trial in six tertiary, teaching hospitals in China between May 12, 2008 and Dec 22, 2010. Eligible patients admitted in ICU with severe sepsis were randomly allocated by a central randomization center to the control group or Tα1 group (1:1 ratio). The primary outcome was death from any cause and was assessed 28 days after enrollment. Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment (SOFA) and monocyte human leukocyte antigen-DR (mHLA-DR) on day 0, 3, 7 in both groups. All analyses were done on an intention-to-treat basis., Results: A total of 361 patients were allocated to either the control group (n = 180) or Tα1 (n = 181) group. The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0% and 35.0% respectively with a marginal P value (nonstratified analysis, P = 0.062; log rank, P = 0.049); the relative risk of death in the Tα1 group as compared to the control group was 0.74 (95% CI 0.54 to 1.02). Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 (mean difference in mHLA-DR changes between the two groups was 3.9%, 95% CI 0.2 to 7.6%, P = 0.037) and day 7 (mean difference in mHLA-DR changes between the two groups was 5.8%, 95% CI 1.0 to 10.5%, P = 0.017) than in the control group. No serious drug-related adverse event was recorded., Conclusions: The use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis., Trial Registration: ClinicalTrials.gov NCT00711620.

Background: Initial poor graft function (IPGF) following orthotopic liver transplantation is a major determinant of postoperative survival and morbidity. Lactate clearance is a good marker of liver function. In this study, we investigated the clinical utility of early lactate clearance as an early and accurate predictor for IPGF following liver transplantation., Methods: This was a prospective observational study of 222 patients referred to the surgical intensive care unit (SICU) after orthotopic liver transplantation. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1500 IU/L within 72 hours after orthotopic liver transplantation. Early lactate clearance was defined as lactate at SICU presentation (hour 0) minus lactate at hour 6, divided by lactate at SICU presentation. The model for end-stage liver disease (MELD) score, Child-Pugh score and laboratory data including AST, ALT, total bilirubin (TB) and prothrombin time (PT) were recorded at SICU presentation and compared between the non-IPGF and IPGF groups. Receiver operating characteristic (ROC) curves were plotted to measure the performance of early lactate clearance, MELD score, Child-Pugh score, TB and PT., Results: IPGF occurred in 45 of the 222 patients (20.3%). The early lactate clearance in the non-IPGF group was markedly higher than that in the IPGF group (43.2+/-13.8% vs 13.4+/-13.7% P<0.001). The optimum cut-off value for early lactate clearance predicting IPGF was 24.8% (sensitivity 95.5%, specificity 88.9%). The area under the curve of the ROC was 0.961, which was significantly superior to MELD score, Child-Pugh score, TB and PT. Patients with early lactate clearance ≤24.8% had a higher IPGF rate (OR=169) and a higher risk of in-hospital mortality (OR=3.625)., Conclusions: Early lactate clearance can serve as a prompt and accurate bedside predictor of IPGF. Patients with early lactate clearance less than 24.8% are associated with a higher incidence of IPGF.

Objective: To study the clinical effect and long-term evaluation of immunomodulation therapy on trauma, severe sepsis and multiple organ dysfunction syndrome (MODS) patients., Methods: Prospective, randomized, blind and controlled clinical analysis of 70 patients conforming to the enrolled standard was carried out. They were divided into two groups at random. One was control group (n=34) with regular therapy, and the treatment group (n=36) with ulinastatin plus thymosin-alpha1 on the base of regular therapy for 1 week. The immunological indexes were determined before and after therapy on the 1 st, 3 rd, 7 th, 14 th and 28 th day, including the changes in lymphocyte count, CD14(+) monocytes human leukocyte antigen (locus) DR (HLA-DR), clinical data and long-term follow-up., Results: During hospitalization, 20 patients died in the control group and 13 patients died in the treatment group. There was significant difference between two groups (P<0.05). After 7 up to 28 days of therapy, the counts of lymphocyte and CD14(+) monocytes HLA-DR were significantly higher than those in control group (all P<0.05). The duration of using mechanical ventilation and pressor agent in the treatment group were shorter than those in the control group (both P<0.01). The length of stay and the cost in the intensive care unit (ICU) were not significantly increased in the treatment group (both P>0.05). The long-term survival time in the treatment group was much longer than that in the control group (P<0.05)., Conclusion: Immunomodulation therapy can improve the prognosis of trauma, severe sepsis and MODS patients in a period of 28 days of observation, and lymphocyte counts and CD14(+) monocytes HLA-DR were increased significantly, showing that immunosuppression can be ameliorated. Immunomodulation therapy can shorten the time of mechanical ventilation and the use of pressor agent, and it does not increase the length of stay and the cost in ICU, and therefore the cost-effectiveness is high. It also can prolong the long-term survival time. The results show that immunomodulation therapy is one of successful therapeutic strategies in the care of critical illness.